After fertilization, remodeling of the oocyte and sperm genomes is essential to convert these highly differentiated and transcriptionally quiescent cells into early cleavage-stage blastomeres that are transcriptionally active and totipotent. This developmental transition is accompanied by cell cycle adaptation, such as lengthening or shortening of the gap phases G1 and G2. However, regulation of these cell cycle changes is poorly understood, especially in mammals. Checkpoint kinase 1 (CHK1) is a protein kinase that regulates cell cycle progression in somatic cells. Here, we show that CHK1 regulates cell cycle progression in early mouse embryos by restraining CDK1 kinase activity due to CDC25A phosphatase degradation. CHK1 kinase also ensures the long G2 phase needed for genome activation and reprogramming gene expression in two-cell stage mouse embryos. Finally, Chk1 depletion leads to DNA damage and chromosome segregation errors that result in aneuploidy and infertility.

• Klíčová slova
• CDC25A phosphatase, CDK1 kinase, CHK1 kinase, cell cycle regulation, early mouse embryos,
• Publikační typ
• časopisecké články MeSH

After fertilization, remodeling of the oocyte and sperm genome is essential for the successful initiation of mitotic activity in the fertilized oocyte and subsequent proliferative activity of the early embryo. Despite the fact that the molecular mechanisms of cell cycle control in early mammalian embryos are in principle comparable to those in somatic cells, there are differences resulting from the specific nature of the gene totipotency of the blastomeres of early cleavage embryos. In this review, we focus on the Chk1 kinase as a key transduction factor in monitoring the integrity of DNA molecules during early embryogenesis.

• Klíčová slova
• Chk1 kinase, DNA damage, cell cycle checkpoint, cleaving embryo,
• MeSH
• checkpoint kinasa 1 * metabolismus   MeSH
• embryo savčí enzymologie   MeSH
• embryonální vývoj * genetika   MeSH
• poškození DNA * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• checkpoint kinasa 1 * MeSH

Tens of thousands of rapidly evolving long non-coding RNA (lncRNA) genes have been identified, but functions were assigned to relatively few of them. The lncRNA contribution to the mouse oocyte physiology remains unknown. We report the evolutionary history and functional analysis of Sirena1, the most expressed lncRNA and the 10th most abundant poly(A) transcript in mouse oocytes. Sirena1 appeared in the common ancestor of mouse and rat and became engaged in two different post-transcriptional regulations. First, antisense oriented Elob pseudogene insertion into Sirena1 exon 1 is a source of small RNAs targeting Elob mRNA via RNA interference. Second, Sirena1 evolved functional cytoplasmic polyadenylation elements, an unexpected feature borrowed from translation control of specific maternal mRNAs. Sirena1 knock-out does not affect fertility, but causes minor dysregulation of the maternal transcriptome. This includes increased levels of Elob and mitochondrial mRNAs. Mitochondria in Sirena1-/- oocytes disperse from the perinuclear compartment, but do not change in number or ultrastructure. Taken together, Sirena1 contributes to RNA interference and mitochondrial aggregation in mouse oocytes. Sirena1 exemplifies how lncRNAs stochastically engage or even repurpose molecular mechanisms during evolution. Simultaneously, Sirena1 expression levels and unique functional features contrast with the lack of functional importance assessed under laboratory conditions.

• MeSH
• genový knockout MeSH
• krysa rodu Rattus MeSH
• messenger RNA genetika   MeSH
• mitochondrie genetika   ultrastruktura   MeSH
• myši MeSH
• oocyty růst a vývoj   metabolismus   ultrastruktura   MeSH
• polyadenylace genetika   MeSH
• RNA dlouhá nekódující genetika   MeSH
• RNA mitochondriální genetika   MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA MeSH
• mitochondrial messenger RNA MeSH Prohlížeč
• RNA dlouhá nekódující MeSH
• RNA mitochondriální MeSH

Homologous chromosome segregation during meiosis I (MI) in mammalian oocytes is carried out by the acentrosomal MI spindles. Whereas studies in human oocytes identified Ran GTPase as a crucial regulator of the MI spindle function, experiments in mouse oocytes questioned the generality of this notion. Here, we use live-cell imaging with fluorescent probes and Förster resonance energy transfer (FRET) biosensors to monitor the changes in Ran and importin β signaling induced by perturbations of Ran in mouse oocytes while examining the MI spindle dynamics. We show that unlike RanT24N employed in previous studies, a RanT24N, T42A double mutant inhibits RanGEF without perturbing cargo binding to importin β and disrupts MI spindle function in chromosome segregation. Roles of Ran and importin β in the coalescence of microtubule organizing centers (MTOCs) and MI spindle assembly are further supported by the use of the chemical inhibitor importazole, whose effects are partially rescued by the GTP hydrolysis-resistant RanQ69L mutant. These results indicate that RanGTP is essential for MI spindle assembly and function both in humans and mice.

• Klíčová slova
• RanGTP, importazole, importin β, meiosis I, oocyte,
• MeSH
• aparát dělícího vřeténka fyziologie   MeSH
• beta karyoferiny genetika   metabolismus   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• meióza fyziologie   MeSH
• mikrotubuly metabolismus   MeSH
• mutace MeSH
• myši MeSH
• oocyty cytologie   metabolismus   MeSH
• proteiny buněčného cyklu genetika   metabolismus   MeSH
• Ran protein vázající GTP genetika   metabolismus   MeSH
• segregace chromozomů MeSH
• výměnné faktory guaninnukleotidů genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• beta karyoferiny MeSH
• jaderné proteiny MeSH
• proteiny buněčného cyklu MeSH
• Ran protein vázající GTP MeSH
• Rcc1 protein, mouse MeSH Prohlížeč
• výměnné faktory guaninnukleotidů MeSH

• Klíčová slova
• DNA damage response, checkpoint, meiosis, oocyte,
• MeSH
• kontrolní body M fáze buněčného cyklu genetika   MeSH
• lidé MeSH
• meióza genetika   MeSH
• oocyty růst a vývoj   metabolismus   MeSH
• oprava DNA genetika   MeSH
• poškození DNA genetika   MeSH
• savci MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• úvodníky MeSH